Characterization of 5? untranslated regions of the voltage-gated sodium channels SCN1A, SCN2A, and SCN3A and identification of cis-conserved noncoding sequences

• Type of Material: Article
• Authors: Melinda S. Martin, Emory University; Bin Tang, Emory University; Nga Ta, Emory University; Andrew Escayg, Emory University
• Language: English
• Date: 2007-08
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2007 Elsevier Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ygeno.2007.04.006
• Title of Journal or Parent Work: Genomics
• ISSN: 0888-7543
• Volume: 90
• Issue: 2
• Start Page: 225
• End Page: 235
• Grant/Funding Information: This work was supported by NIH Research Grant NS051834 (A.E.).
• Keywords: sodium channel; 5′ untranslated region; conserved sequence; SCN1A; sequence alignment; SCN3A; gene expression regulation; epilepsy; SCN2A
• Research Categories: Biology, Neuroscience; Health Sciences, Human Development

Abstract

The human voltage-gated sodium channel gene cluster on chromosome 2q24 contains three paralogs, SCN1A, SCN2A, and SCN3A, which are expressed in the central nervous system. Mutations in SCN1A and SCN2A cause several subtypes of idiopathic epilepsy. Furthermore, many SCN1A mutations are predicted to reduce protein levels, emphasizing the importance of precise sodium channel gene regulation. To investigate the genetic factors that regulate the expression of SCN1A, SCN2A, and SCN3A, we characterized the 5′ untranslated region of each gene. We identified multiple noncoding exons and observed brain region differences in the expression level of noncoding exons. Comparative sequence analysis revealed 33 conserved noncoding sequences (CNSs) between the orthologous mammalian genes, and six CNSs between the three human paralogs. Seven CNSs corresponded to noncoding exons. Twelve CNSs were evaluated for their ability to alter the transcription of a luciferase reporter gene, and three resulted in a modest, but statistically significant change.